The molecular mechanism of the psoralen(furocoumarins) photosensitization is believed to involve photochemical modification of DNA via covalent photocoupling of psoralens to pyrimidine bases forming cyclobutane type monoadducts and diadducts leading to the DNA crosslinking. These reactions have been extensively studied. However, the photoaddition of psoralen to poly A is quite efficient and one adenine base in E. coli tRNA is involved in photoaddition by 8-methoxypsoralen. The nature of this photoaddition reactions between the excited psoralen and purine bases are not understood at all and the structure of the adducts are not characterized yet even though it is essential to understand the molecular mechanism of the psoralen photosensitization. No direct chemical or structural proof for psoralen-purine base cross-adducts has been reported in the literature. Chemical characterization of photoadducts formed from the following experiments will be carried out. Photoaddition of DMC and 8-MOP to adenosine, Photoaddition of DMC, 8-MOP, and AMT to poly(A) and poly(dA). Because of the high photoreactivity of psoralen toward adenine base, it is possible to probe the poly(dA) sequences in DNA, especially in DNA's of eukaryotic origin, where many satellite DNA's and specific regulatory genes contain varying degrees of poly(da) sequences. In order to fully exploit the possible base- and base-sequence specific modifications of DNA with psoralens, we plan to characterize poly(dA)-psoralen photolyzates. Thus, the long term objectives of this study are to delineate whether psoralens and DMC can be developed as base and base sequence specific probes for DNA and RNA and to elucidate the photosensitizing and phototherapeutic potency of psoralens at the molecular level.